Dr. Nicholas Abend is an Assistant Professor of Neurology and Pediatrics at the University of Pennsylvania (U Penn) and the Children's Hospital of Philadelphia (CHOP). Dr. Abend has completed initial studies demonstrating that non-convulsive seizures (NCS) are common in critically ill children with acute encephalopathy. However, their impact on physiology and outcome is unknown. As a natural extension of this work, his short-term goal is to conduct mentored research on critically ill children focused on the impact of NCS on cerebral physiology and neuro-developmental outcome, and to gain research training related to outcomes research and non-invasive optical imaging of cerebral physiology. His long-term goal is to become an independent investigator leading multi-disciplinary investigations of multi-modality physiologic monitoring and management to improve the neuro-developmental outcome of critically ill children. Research: Dr. Abend proposes three linked aims: (1) Develop a valid seizure burden metric that accounts for NCS anatomical extent and duration. This metric can be used by future studies evaluating the neurodevelopmental impact and optimal management of NCS. (2) Perform a prospective study to determine whether NCS and non-ictal rhythmic discharges (RD) have a detrimental impact on cerebral physiology, as measured by non-invasive optical imaging of cerebral blood flow and oxygenation. Discovery of a causal mechanism by which some NCS and RD could worsen outcome would suggest that NCS and RD detection and management could improve outcome. Additionally, rather than relying on standardized nomenclature to categorize RD based on electrographic appearance, RD could be categorized more physiologically. (3) Perform a prospective study evaluating the impact of NCS on neuro-developmental outcome. An association between NCS and worse neuro-developmental outcome would suggest that NCS identification and management could improve outcome. Dr. Abend will investigate children resuscitated from cardiac arrest, providing a singular etiology suitable for study. However, since NCS occur in a large number of critically ill children and adults with a wide variety of acute encephalopathies, extensions of this work may improve the outcome of many critically ill patients. Environment and Career Development: The scientific and career development plans build upon a mentorship and research infrastructure at CHOP and U Penn that has already made Dr. Abend very productive. This training network will be enhanced by additional mentors and collaborators, extensive one-on-one training in optical imaging acquisition and analysis, courses within the Center for Epidemiology and Biostatistics and The Neuroscience Institute (focused on clinical research, outcomes research, biostatistics, neuroprotection, and research ethics), and participation in a wide array of research conferences. Dr. Abend's mentorship team has extensive experience in NIH funded clinical research, a track record of training successful independent investigators, and a commitment to Dr. Abend's development into an independent researcher and international leader. The combination of expert mentorship, a well-developed clinical research infrastructure, and extensive didactic training will assure Dr. Abend's developing into an effective neuroscientist working to improve the outcome of treatment of critically ill children. Summary: The scientific and career development plans will provide an excellent patient-oriented research experience with world-class mentorship in an outstanding environment. Completion of these plans will provide Dr. Abend with the scientific and methodological foundation to conduct independent research focused on real-time multi-modal neuro-monitoring, which has the potential to reduce neurologic injury in critically ill patients. PUBLIC HEALTH RELEVANCE: Non-convulsive seizures are common in children with neurocritical illness, but their impact on brain physiology and neuro-developmental outcome is unknown. This proposal will determine: (1) how to best quantify non-convulsive seizures, (2) whether non-convulsive seizures and related non-ictal rhythmic discharges impact brain physiology as measured by a non-invasive optical imaging technique, and (3) whether non-convulsive seizures are associated with worse neuro-developmental outcome. Improved understanding of the impact of non-convulsive seizures on cerebral physiology and neuro-developmental outcome will improve the care of critically ill patients.